Ultraconserved long non-coding RNA uc 112 is highly expressed in childhood T versus B-cell acute lymphoblastic leukemia

ABSTRACT Aberrant expression of long non-coding RNAs (lncRNAs) has been detected in several types of cancer, including acute lymphoblastic leukemia (ALL), but lncRNA mapped on transcribed ultraconserved regions (T-UCRs) are little explored. The T-UCRs uc.112, uc.122, uc.160 and uc.262 were evaluated by quantitative real-time PCR in bone marrow samples from children with T-ALL (n = 32) and common-ALL/pre-B ALL (n = 30). In pediatric ALL, higher expression levels of uc.112 were found in patients with T-ALL, compared to patients with B-ALL. T-cells did not differ significantly from B-cells regarding uc.112 expression in non-tumor precursors from public data. Additionally, among B-ALL patients, uc.112 was also found to be increased in patients with hyperdiploidy, compared to other karyotype results. The uc.122, uc.160, and uc.262 were not associated with biological or clinical features. These findings suggest a potential role of uc.112 in pediatric ALL and emphasize the need for further investigation of T-UCR in pediatric ALL.

Childhood T-cell acute lymphoblastic leukemia in a single Latin American center: impact of improved treatment scheme and support therapy on survival

ABSTRACT Background and objective T-cell acute lymphoblastic leukemia (T-ALL) in children represents a high-risk disease. There is a lack of studies assessing the outcome of T-ALL in Hispanic populations, in which it is a rare malignancy. We report the characteristics and results of treatment for childhood T-cell ALL in children over 14 years at a Latin American reference center. Material and methods From January 2005 to December 2018, there occurred the analysis of twenty patients ≤ 16 years of age from a low-income open population diagnosed at a university hospital in Northeast Mexico. Clinical and laboratory characteristics, treatment regimens and outcomes were assessed by scrutinizing clinical records and electronic databases. Diagnosis was confirmed by flow cytometry, including positivity for CD-2, 5, 7 and surface/cytoplasmic CD3. Survival rates were assessed by the Kaplan-Meier method. Results There was a male preponderance (70 %), with a 2.3 male-to-female ratio (p= .074), the median age being 9.5 years. Leucocytes at diagnosis were ≥ 50 × 109/L in 13 (65 %) children, with CNS infiltration in 6 (30 %) and organomegaly in 10 (50 %). The five-year overall survival (OS) was 44.3 % (95 % CI 41.96-46.62), significantly lower in girls, at 20.8 % (95 % CI 17.32-24.51) vs. 53.1 % (95 % CI 50.30-55.82), (p= .035) in boys; there was no sex difference in the event-free survival (EFS) (p= .215). The survival was significantly higher after 2010 (p= .034). Conclusion The T-cell ALL was more frequent in boys, had a higher mortality in girls and the survival has increased over the last decade with improved chemotherapy and supportive care.

Treatment outcomes of children with acute lymphoblastic leukemia in a middle-income developing country: high mortalities, early relapses, and poor survival / Desfechos do tratamento de crianças com leucemia linfoblástica aguda em um paísem desenvolvimento de renda média: altas taxas de mortalidade, recidivas precocese baixa sobrevida

Abstract Objective Acute lymphoblastic leukemia is the most common childhood cancer, yet surprisingly, very few studies have reported the treatment outcomes and the relapse rate of patients from low/middle-income countries. Method This study was a 5-year retrospective cohort study. It was conducted at Oncology Center of Mansoura University in Egypt and aimed to estimate the treatment outcomes and the relapse rates of newly diagnosed acute lymphoblastic leukemia in children. Results Two hundred children suffering from acute lymphoblastic leukemia were studied; forty-six patients (23%) died during induction and most of those deaths were related to infection. Forty-one patients (27%) relapsed out of the 152 patients who achieved complete remission. The most common site of relapse was the bone marrow, followed by the isolated central nervous system, 53.7% and 31.7%, respectively. Seventy-eight percent of relapses occurred very early/early rather than later. The majority of relapse patients' deaths were related to infection and disease progression. The 5-year overall survival rate for patients was 63.1% (82.1% for non-relapsed compared to 36.6% for relapsed patients). Conclusion There was a high incidence of induction deaths related to infection and high percentages of very early/early relapses, with high mortalities and low 5-year overall survival rates. These findings suggest the urgent need for modification of chemotherapy regimens to be suitable for the local conditions, including implementation of supportive care and infection control policies. There is also a requirement for antimicrobial prophylaxis during induction period combined with the necessary increase in government healthcare spending to improve the survival of acute lymphoblastic leukemia in Egyptian children.

Resumo Objetivo Estimar os desfechos do tratamento e as taxas de recidiva de crianças recém-diagnosticadas com leucemia linfoblástica aguda. É o câncer infantil mais comum, mas surpreendentemente poucos estudos relataram os desfechos do tratamento e a taxa de recidiva em pacientes de países de renda baixa/média. Método Estudo de coorte retrospectivo de cinco anos. Foi feito no Centro de Oncologia da Universidade de Mansoura, no Egito. Resultados Foram estudadas 200 crianças com leucemia linfoblástica aguda, das quais 46 (23%) morreram durante a indução e a maioria dessas mortes estava relacionada à infecção. Dos 152 pacientes que alcançaram a remissão completa, 41 (27%) apresentaram recidiva. O local mais comum de recidiva foi a medula óssea, seguido pelo sistema nervoso central isolado, com 53,7% e 31,7% dos casos, respectivamente. Das recidivas, 78% ocorreram muito precocemente ou precocemente, em vez de tardiamente. A maioria das mortes de pacientes com recidiva estava relacionada à infecção e progressão da doença. A taxa de sobrevida global em cinco anos para os pacientes foi de 63,1% (82,1% para não recidivados em comparação com 36,6% para os recidivados). Conclusão Houve uma alta incidência de mortes na indução relacionadas à infecção e altos percentuais de recidivas muito precoces ou precoces, com altas taxas de mortalidade e baixas taxas de sobrevida global em cinco anos. Nossos achados sugerem a necessidade urgente de modificação dos esquemas quimioterápicos para adequação às nossas condições locais, implantação de políticas de cuidados de suporte e controle de infecções. Há também a necessidade de profilaxia antimicrobiana durante o período de indução, junto com um aumento necessário nos gastos governamentais com a saúde, para melhorar a capacidade de sobrevivência das crianças egípcias com leucemia linfoblástica aguda.

Método de reação em cadeia por polimerase para a pesquisa de retrovírus em casos de linfomas não-Hodgkin de células T periféricas e paraparesias crurais espásticas / PCR methods for retrovirus search in cases of non-Hodgkin lynphoma of peripheral T-cells and crural spastic paraparesis

Partindo de dois oligonucleotídeos degenerados derivados de uma fração conservada da região pol de retrovírus conhecidos, foi pesquisada a presença de agente viral exógeno ou de uma seqüência endógena similar as retrovirais (ERV). A partir da amplificação do DNA pela técnica de PCR, foram testadas células mononucleares periféricas de 33 portadores de paraparesia crural espática de evolução crônica sem agente etiológico conhecido, produzindo um fragmento de aproximadamente 500 bp em 8 destas amostras...

Leucemias agudas como neoplasias secundarias em criancas portadoras de linfomas avancados / Acute leukemias as secondary neoplasms in advanced childhood non-Hodgkin's lymphoma

Em 1985 foi iniciado, no Instituto da Crianca-HC-FMUSP, um programa terapeutico para linfomas nao Hodgkin, com resultados claramente superiores aos anteriormente obtidos no Servico. Sao descritos dois casos de pacientes que apresentaram neoplasias secundarias, e sua possivel implicacao com as drogas empregadas.